Host-cell dependent epigenetic profiles associated with survival outcomes in T. gondii infection

Toxoplasmosis is a widespread parasitic disease affecting roughly one-third of the global population. In immunocompromised individuals or during pregnancy, infection can result in severe complications. Following primary infection, Toxoplasma gondii forms dormant bradyzoite cysts in tissues such as the brain and eyes. These cysts can rupture, particularly in immunocompromised hosts, releasing active parasites and triggering recrudescence. Efforts to experimentally induce and study bradyzoite cyst recrudescence have been hindered by the limited capacity of cell culture adapted strains to form tissue cysts in vivo. T. gondii employs diverse strategies to persist within host cells, including manipulation of host metabolism and immune responses, and these strategies may vary by host cell type. Here, we profiled epigenomic and transcriptomic features associated with differential parasite survival in distinct cell types. Using an ex vivo model of the Type II ME49 strain unadapted to fibroblast culture, we compared parasite survival and epigenetic profiles in neonatal mouse astrocytes (AST) and human foreskin fibroblasts (HFF). Comparative analyses revealed marked divergence in parasite population dynamics, accompanied by reduced H3K4me3 enrichment at promoter regions in parasites grown in HFF. This epigenetic shift correlated with transcriptomic changes in genes linked to cell cycle progression, growth, and development, including a subset of AP2 transcription factors, underscoring the influence of host cell type on parasite biology.